EP2240228B1

EP2240228B1 - Dry powder inhaler

Info

Publication number: EP2240228B1
Application number: EP09708677A
Authority: EP
Inventors: Stephen T. Dunne
Original assignee: Boehringer Ingelheim Pharma GmbH and Co KG
Current assignee: Boehringer Ingelheim Pharma GmbH and Co KG
Priority date: 2008-02-05
Filing date: 2009-02-02
Publication date: 2012-03-28
Anticipated expiration: 2029-02-02
Also published as: GB0802028D0; ATE551088T1; WO2009098010A1; US20100326438A1; EP2240228A1; US10112019B2; EP2240228B2

Abstract

An inhaler for use with a dry powder pharmaceutical formulation, including: a chamber containing the dry powder formulation, a valve disposed in series with the chamber for regulating air flow through the chamber, and a bypass coupled around the combination of the chamber and the valve, where the valve and bypass cooperate for ensuring that the air flow is at least essentially fixed or kept constant or at a minimum accepted or desired or required flow rate through the chamber, and for varying air flow restriction through the inhaler with flow rate, or for keeping the air flow restriction generally constant.

Description

This invention is concerned with dry powder inhalers for the delivery of drugs to the lungs. In particular, the present invention relates to an inhaler with a chamber containing a medicament or inhalation formulation in the form of powder. The powder is discharged by means of a gas or air stream flowing through the chamber to entrain the powder and to generate or form a powder spray for inhalation.
Many dry powder inhalers are on the market or have been proposed. There are two main types; passive and active. In passive devices all the energy required for deagglomeration the powder and transferring the powder to the lungs is provided by the patient. Most powder inhalers are of the passive type where the powder is inhaled by the patient without the aid of a secondary energy source.
Dry powder inhalers are subdivided into single dose devices and multi dose devices. Multi dose inhalers are further subdivided into pre metered types where the doses are stored individually in the device and metering devices where the powder dose is metered in the device.
Multi dose pre metered devices have the advantage that the single doses are metered under strict factory conditions and the powder can quite easily be isolated from the atmosphere. In many applications the active drug powder is mixed with a carrier such as lactose which tends to absorb humidity from the atmosphere which makes it stick together and difficult to de-agglomerate.
US 7 305 986 B1 discloses a passive inhaler with a storage section which holds several two-part capsules containing dry powder medicament. For usage a capsule is loaded into a mixing section consisting of a configured Venturi chamber. For use the mouthpiece is extended by rotation. As the mouthpiece is connected by a swivel joint to the mixing section, this rotation is partly transferred to the capsule. Thereby the two halves are rotated around their longitudinal axes with respect to each other and apertures in each half are aligned allowing air to pass through the capsule, releasing the medicament contained therein. The rate of air flow is controlled in the intake section of the inhaler so that the air flows at a sufficient rate. For this, the intake port only opens when the user generates a sufficient vacuum in his lungs.
WO 01/00263 A2 discloses a passive aerosolization device in which powdered medicament is extracted from a receptacle using a patient's inspired respiratory gases. The system comprises a threshold valve - different types are disclosed - and a regulation system which ensures that the gas flow leaving the receptacle has got an acceptable flow rate so that the aerolized medicament may properly pass into the patient's lungs. In one device receptacles are inserted, each receptacle comprising a receptacle body with a chamber holding the powdered medicament and with a threshold valve. The flow of respiratory gases through the device is prevented until the user creates sufficient vacuum to open the threshold valve.
One of the main advantages of active inhalers is that the delivered mass or dose of powder is independent from the flow generated by the user which is generally accepted to be in the range of between 20 to 60 liters per minute. US2007/0240714 A1 discloses an active dispensing device in which pressurized gas is used to force powder out of a storage chamber through a duct to generate a spray. The gas pressure is either provided by an air pump or by a container with pressurized gas. If liquefied gas or a container with pressurized gas is used the pressure may be reduced by a regulator before supplying the gas to the storage chamber.
The disadvantage of passive inhalers that the delivered mass or dose varies according to the airflow generated by the user. The present invention is a device that minimizes variations of delivered mass or dose with airflow variations.
Metering powder inhalers have a metering chamber for accurately metering the dose to be delivered while pre metered inhalers have pre-metered doses in capsules or blister or other chambers. For simplification both types will be called metering chambers in this specification. Most passive powder inhalers have a primary flow path for the air that goes through the metering chamber and carries the powder to the patient and a secondary flow path or bypass where the air does not go through the powder-metering chamber.
WO 03/000329 A2 discloses an aerolization device with a mouthpiece, and a flow path arrangement in fluid communication with the mouthpiece and with a region in the housing adapted to hold a powder. The flow path arrangement has a flow regulating valve and a threshold valve, where the threshold valve is configured to open at a first vacuum level and to close at a second vacuum level that is less than the first vacuum level. The flowrate of the air drawn through the mouthpiece is regulated by the flow regulating valve to remain within a certain range while the threshold valve remains open. The flow regulating valve is in a second flow path and used maintain a constant flow rate through the whole flow path arrangement by increasing the flow resistance.
When the airflow through the chamber containing the powder varies, deagglomeration of the powder and spray generation vary as well. Consequently, the spray characteristics and the amount of outputted powder may very significantly.
Object of the present invention is to provide an inhaler with improved discharge characteristics.
The above object is achieved by an inhaler according to claim 1. Preferred embodiments are subject of the subclaims.
According to the present invention, the inhaler comprises at least one valve for regulating flow through the chamber with powder, for ensuring that airflow is at least essentially fixed through the chamber, for varying the airflow restriction with flow rate, and/or for keeping the airflow restriction generally constant This allows to improve the discharge characteristics, in particular in passive inhalers where the discharge characteristics of the inhaler greatly depend on the breathing in of the respective user or patient, i.e. of the total flow rate of air through the inhaler.
In particular, the present invention relates to a valve that keeps the airflow through the metered drug formulation at least essentially constant ensuring a constant delivery of powder to the patient. To do this the valve is dimensioned so that at the minimum accepted flow rate (20 liters/minute) enough air reaches the metering chamber. For devices with bypasses as the flow rate increases with different users or even with the same user more air is forced to go via the bypass.
For devices with bypasses the valve may be located in the primary flow path or the bypass. When in the primary flow path the valve restricts flow or closes with increased total flow and if in the by pass the reverse happens. For inhalers with by passes the device may have a valve in both the primary and by pass flow paths.
With devices with bypasses the pressure drop or restriction across the device is kept generally constant.
For devices without bypasses the valve is located in the primary flow path. In this case the device flow restriction varies with flow rate.
The valve may be operated automatically or pre adjusted by the user or other depending on the inhalation capacity of the user.
Preferably the valve or valves are located upstream of the powder chamber to eliminate powder losses on valve surfaces.
Many valve types may be used; spring loaded plungers, electronic controlled valves, rubber slit valves that close or open with increasing flow pressure or any other type of flow regulating valve.
Further aspects and features of the present invention will be apparent from the claims and from the following description referring to the drawings. In the drawings, it shows:

Fig. 1: a schematic diagram of an inhaler according to a first embodiment of the present invention;
Fig. 2: a schematic diagram of an inhaler according to a second embodiment of the present invention;
Fig. 3: a schematic representation of a valve for an inhaler according to the present invention; and
Fig. 4: a schematic view of a reservoir for an inhaler according to the present invention.

In the following, not all possible embodiments are shown. It must be understood that other embodiments are possible based on the invention.
In Fig. 1 a schematic of an inhaler I with a valve 6 in a primary flow path is shown. Air is drawn into the inhaler I via an inlet 1 of the inhaler I and delivered to the patient at point 2. A metering chamber 3 has powder 4 within. A bypass 5 connects inlet 1 to outlet 2.
The inhaler I comprises the inlet 1 where air can be drawn into the inhaler I. At least part of the air can flow through the chamber 3 containing the powder 4 (to entrain and discharge the powder 4). The mixture of air and powder is discharged via point 2 which represents in particular an outlet or nozzle of the inhaler I.
The chamber 3 may contain a pre-metered dose of the powder 4 or may be used to meter the powder 4 in particular of a bulk storage of powder 4 (not shown). The inhaler I may comprise multiple chambers 3 with pre-metered doses of powder 4 and/or a reservoir R as shown in Fig. 4, in particular a blister strip or carrier with multiple chambers 3 respectively containing a dose of the powder 4.
The total flow 8 generated by the patient is split between the primary flow 8a and bypass flow 8b. A valve 6 ensures that flow 8a through the chamber 3 is at least essentially fixed by restricting flow 8a and increasing flow 8b when total flow 8 increases.
The primary flow 8a is the part of the total flow 8 of air that is flowing through the chamber 3. The bypass flow 8b is the other part of the total flow 8 of air that is flowing through the bypass 5.
The valve 6 is located streamup of the chamber 3 in the primary flow path, i.e. in the flow path of the chamber 3. The bypass 5 branches from the main flow path coming from inlet 1 streamup of valve 6. However, other arrangements are possible as well. The valve 6 may be adjusted by the user or any other person or be an automatic valve such as described in Fig. 3.
Preferably, the inhaler I or valve 6 is dimensioned or constructed such that the primary flow 8a is kept or regulated at least essentially to a desired or required (minimum) primary flow rate 8a of air through the chamber 3. This desired or required primary flow rate is in particular less than 30 liters/min, in particular about 20 liters/min.
If the user or patient draws more air through the inhaler 1, i.e. if the total flow rate 8 is higher, the amount exceeding the required or desired primary flow rate 8a is at least essentially directed as bypass flow 8b through the bypass 5 in the shown embodiment.
Preferably, the inhaler I or valve 6 is constructed or dimensioned such that the pressure drop over the inhaler I (i.e. between inlet 1 and outlet 2) is kept at least essentially constant.
It is also possible to omit the bypass 5. In this case, the valve 6 preferably significantly increases the total flow restriction, i.e. the flow restriction of the inhaler 1, when the desired or required primary flow rate 8a through the chamber 3 is approached or reached or exceeded. Thus, the airflow through the chamber 3 and the total airflow can be kept essentially or better constant than without valve 6.
In the following, a second embodiment of the inhaler I will be explained with reference to Fig. 2. The previous description applies preferably in a similar manner even if not repeated.
In Fig. 2 shown a schematic view of an inhaler I with a valve 16 in the bypass flow path. Air is drawn into the inhaler via inlet 11 and delivered to the patient at point 12. A metering chamber 13 has powder 14 within. A bypass 15 connects inlet 11 to outlet 12. The total flow 18 generated by the patient is split between the primary flow 18a and bypass flow 18b. The valve 16 ensures that flow 18a through the chamber 13 is fixed by restricting flow 18b through the bypass 15 when total flow 18 decreases. The valve 16 may be adjusted by the user or any other person or be an automatic valve.
The second embodiment can behave similar to the first embodiment with bypass 5.
It is also possible to provide a valve 6 in the primary flow path in addition to the valve 16 in the bypass path as shown by dashed lines in Fig. 2. Thus, an even better control of the flow rates is possible.
The valve 6 or 16 may be a (automatic) flow regulating valve or (depending on the flow characteristics of the inhaler I or the construction with or without bypass 5 / 15) a pressure regulating valve.
In Fig. 3, an example of the automatic flow regulating valve 6 is shown for use in the primary airflow 8a or 18a. A body 21 of the valve 6 has a passageway 26 with a shoulder 24. A preferably conical plunger 22 is moveable and/or mounted on a spring 23. The plunger 22 forms a gap 28 between shoulder 24 and plunger 22. The air flows in the direction of arrow 25. As the airflow 25 tries to increase pressure on plunger 22, this forces the plunger 24 to move towards shoulder 24 closing gap 28 restricting the flow and keeping it relatively constant at all times.
Preferably, the inhaler I and/or the valve 6 / 16 work only mechanically. However, it is also possible that the valve 6 or 16 work electronically or in any other manner.
The inhaler I and/or the valve 6 / 16 may be constructed or dimensioned such that the primary air flow 8a through the chamber 3 / 13 is allowed or opened only if a sufficiently high suction force, air pressure and/or bypass air flow 8b / 18b is present or detected.
Fig. 4 shows in a very schematic view a reservoir R of the inhaler I. Preferably, the reservoir can be inserted into the inhaler I. The reservoir R comprises multiple chambers 3/13 respectively containing a dose of powder 4/14. The reservoir R is preferably a blister strip wherein the chambers 3/13 are formed by blisters which can be opened preferably by peeling or piercing and/or one after the other in the inhaler I. However, other constructional solutions are possible as well.

Claims

Inhaler (I) in which air is drawn via an inlet (1, 11) and delivered via a chamber (3, 13) containing powder (4, 14) to an outlet (2,12), the inhaler comprising
- a bypass (5, 15) for bypassing the chamber (3, 13) and for splitting the total air flow (8, 18) between a primary flow (8a, 18a) through the chamber (3,13) and a bypass flow (8b, 18b) through the bypass (5,15) and

- a valve (6,16) for regulating air flow (8a, 18a) through the chamber (3, 13),
characterized in that
the valve ensures an air flow (8a, 18a) that is at least essentially fixed or kept constant through the chamber (3, 13) and
more air is forced to go via the bypass (5, 15) as the total flow rate increases.
Inhaler according to claim 1, characterized in that the valve (6) is located in the primary flow path, in particular wherein the valve (6) restricts flow or closes with increased total flow.
Inhaler according to claim 1, characterized in that the valve (16) is located in the bypass (5, 15), in particular wherein the valve (6) restricts flow or closes with decreased total flow.
Inhaler according to claim 2 or 3, characterized in that a valve (6) is located in the primary flow path and a valve (16) is located in the bypass (5, 15).
Inhaler according to one of claims 2 to 4, characterized in that the pressure drop or restriction across the inhaler (I) is kept generally constant.
Inhaler according to one of the previous claims, characterized in that the valve (6, 16) is dimensioned so that at the minimum accepted flow rate, preferably 20 1/min, enough air reaches the chamber (4, 14).
Inhaler according to one of the previous claims, characterized in that the valve (6, 16) is located upstream of the chamber (3, 13).
Inhaler according to one of the previous claims, characterized in that the valve (6, 16) is a flow regulating valve.
Inhaler according to one of the previous claims, characterized in that the inhaler (I) comprises pre-metered doses of the powder (4, 14) in chambers (3, 13), such as capsules or blisters, preferably in a reservoir (R).
Inhaler according to one of the previous claims, characterized in that the inhaler (I) is a passive dry powder inhaler.
Inhaler according to one of the previous claims, characterized in that the valve (6, 16) comprises a plunger (22) that is biased by means of a spring (25) so that the valve (6, 16) can be closed or restrict flow (25) through the valve (6, 16) when the flow (25) increases the pressure on the plunger (22).
Inhaler according to one of the previous claims, characterized in that the valve (6, 16) can be pre adjusted by the user or other depending on the inhalation capacity of the user.